Excessive galloylated flavanols not only cause instability in the wine but also lead to unbalanced astringency. Although clarification agents are always used to precipitate unstable tannins in wine, the non-specific adsorption of tannins results in the failure to precisely regulate the tannin composition of the wine. In this work, molecularly imprinted polymers (MIPs) with template molecules of galloylated flavanols were designed to specifically adsorb gallotannins to reduce wine astringency. The results showed that the “pores” on the surface of the MIPs are the structural basis for the specific adsorption of the target substances, and the adsorption process is a chemically driven single-molecule layer adsorption. Moreover, in the mono/oligomeric gallotannin-rich model solution, the adsorption of gallotannins by I-MIPs prepared as single template molecules reached 71.0%, and the adsorption capacity of MIPs for monomeric gallotannins was about 6.0 times higher than polymeric gallotannins. Given the lack of technology for the targeted adsorption of tannins from wine, this work explored the targeted modulation of wine astringency by using molecular imprinting techniques.